SPS 2024 -- The Latin square crossover is recommended as best practice for in vivo QT studies. However, an escalating design may instead be required due to long compound half-life, insufficient toxicity data to inform dose level selection, a need to build up tolerance to the test article to enable safe dosing or logistics (e.g., avoiding use of multiple simultaneous inhalation dose generation systems thereby reducing risk of contamination). We have performed ICH E14/S7B Q&A compliant in vivo QT validation studies with oral moxifloxacin using both a Latin square and an ascending dose design in nonhuman primate (NHP), dog and minipig. The objective of this work was to compare the sensitivity of the dosing designs and to generate positive control moxifloxacin QTc data in support of ICH E14/S7B studies when using an ascending dose design. 

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